Our broad objective is to understand inducible cellular responses to DNA damage by carcinogens, many of which are mutagens in bacteria, with special emphasis on understanding the relationship between those responses that contribute to cellular survival following carcinogenic damage and those which affect mutagenesis. We use Escherichia coli as a model cell system in which to study inducible SOS responses and adaptive responses, evidence for both of which has also been found in mammalian cells, because of the advantage of availability of relevant mutants and extensive biochemical and genetic characterization. Immediate research objectives include: (1) Gene products involved in inducible repair of UV damage. Having evidence that long patch repair synthesis may be the primary SOS process effecting enhanced cellular survival, we are attempting to identify the gene products that participate in this process. In particular, the possible involvement of an altered polymerase will be tested and the nature of the requirement for the recA gene will be examined. Whether long patch synthesis proceeds by a mechanism involving the recF pathway will be investigated. (2) Substrate for long patch repair of UV damage. Having evidence suggesting that long patches occur at a small class of damage sites that are refractory to constitutive repair and that are potent blocks to replication, we are investigating the nature of these sites as an approach to understanding the means by which the inducible process contributes to survival. We are particularly interested in the possibility that lesions in some functionally distinct regions of the genome, perhaps growing point regions or actively transcribing genes, are involved. (3) Repair of alkylation damage. Having evidence that SOS induction promotes survival of alkylation damage in addition to UV damage, we are attempting to determine the interaction of the SOS and adaptive responses in excision repair and mutagenesis after treatment with alkylating agents. Effects of the two inducible processes on repair synthesis and on adduct removal will be compared. The possibility that glycosylase action significantly precedes AP endonuclease action in repair of alkylation damage, thereby generating important premutagenic lesions (AP sites) as a consequence of repair, will be examined.